Abstract
BackgroundWe previously showed that enzymatically hydrolyzed Dendropanax morbiferus H. Lév. leaf (Hy-DP) and unripe Rubus coreanus Miq. (5-uRCK) extracts exhibit potent vasodilator effects on isolated aortic rings from rats partly through endothelium-dependent and endothelium-independent mechanisms. These two extracts have different mechanisms of action; however, their combined effect on antihypertensive activity has not been explored.MethodsThe present study aims to investigate the effect of a chronic optimized mixture (HDR-2, composed of Hy-DP and 5-uRCK in a 2:1 mass ratio) on vascular tension and blood pressure in two different hypertensive rat models.ResultsThe results showed that HDR-2 concentration-dependently relaxed endothelium-intact and endothelium-denuded aortic rings precontracted with phenylephrine. Antihypertensive effects were assessed in vivo on a 1 kidney-1 clip (1 K-1C) rat model of hypertension and spontaneously hypertensive rats (SHRs). Acute HDR-2 treatment significantly decreased systolic blood pressure (SBP) 3 h posttreatment in both models. Chronic HDR-2 administration also significantly decreased SBP in the hypertensive rat models. Moreover, HDR-2 increased eNOS protein expression and phosphorylation levels in the aorta.ConclusionChronic HDR-2 administration may effectively improve vascular function by decreasing plasma angiotensin-converting enzyme (ACE) activity and AngII levels. HDR-2 significantly improved acetylcholine (ACh)-induced aortic endothelium-dependent relaxation and affected sodium nitroprusside (SNP)-induced endothelium-independent relaxation in SHRs.
Highlights
We previously showed that enzymatically hydrolyzed Dendropanax morbiferus H
Quercetin and its metabolites, such as 3-(3-hydroxyphenyl)propionic acid (3HPPA), 3,4-dihydroxyphenylacetic acid (DHPA) and 4-methylcatechol (4MC), administered orally are well known to be able to decrease arterial blood pressure [13,14,15]. Another our previous study reported that we developed a technique to increase L-arginine and γ-aminobutyric acid (GABA) levels of Dendropanax morbiferus H. Léveille extract (DP) by enzymatic hydrolysis [16]
We investigated the effects of HDR-2 on Endothelial nitric oxide synthase (eNOS) mRNA expression in Human umbilical vein endothelial cell (HUVEC) and verified that eNOS mRNA levels were significantly increased by HDR-2 treatment (Fig. 2c)
Summary
We previously showed that enzymatically hydrolyzed Dendropanax morbiferus H. (5-uRCK) extracts exhibit potent vasodilator effects on isolated aortic rings from rats partly through endothelium-dependent and endothelium-independent mechanisms. These two extracts have different mechanisms of action; their combined effect on antihypertensive activity has not been explored. High blood pressure is one of the major risk factors for the development of vascular diseases such as atherosclerosis, coronary heart disease and stroke [1], and several studies have reported cardiovascular risks associated. Many antihypertensive therapeutic drugs have been developed and are available for use in clinical treatment, including thiazide diuretics, β-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors and C a2+ channel blockers. Future investigations for novel and safe antihypertensive drugs are still required
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